CD81 expression in peripheral blood lymphocytes before and after treatment with interferon and ribavirin in HIV/HCV coinfected patients

Background

CD81 is expressed on lymphocytes and confers HCV viral infectivity support. The aim of our study was to quantify CD81 expression in peripheral blood B‐ and T‐cells of HCV/HIV‐coinfected patients and healthy subjects to examine its association with several HCV virological characteristics and the therapeutic responsiveness to HCV antiviral treatment.

Methods

We carried out a cross‐sectional study on 122 naïve patients. For a duration of 48 weeks, 24 out of 122 patients underwent HCV antiviral therapy with interferon (IFN)‐α and ribavirin. T‐ and B‐cell subsets were analysed by flow cytometry.

Results

We found that HIV/HCV coinfected patients with HCV‐RNA ≥850 000 IU/mL had lower values of %CD19+CD81‐CD62L+ and %CD19+CD62L+; and higher values of CD19+CD81+CD62L− and CD19+CD81+ percentages and absolute counts than patients with HCV‐RNA <850 000 IU/mL. Similarly, HIV/HCV coinfected patients with the genotype 1 had lower values of %CD19+CD81−CD62L+ and higher values of CD3+CD81+CD62L− and CD3+CD81+ percentages and absolute counts than patients without genotype 1. Moreover, we found that HIV/HCV coinfected patients had higher values of %CD19+HLA‐DR+CD25+, %CD19+CD40+CD25+ and %CD19+CD25+ than healthy control patients. When we studied the B‐ and T‐cell subset kinetics of 24 HIV/HCV coinfected patients on HCV antiviral therapy, we found a significant decrease in CD3+CD81+and CD3+CD81+CD62L− subsets and a significant increase in CD3+CD62L+ and CD3+CD81+CD62L+ percentages and absolute counts, but the variation in these markers disappeared several months after stopping the treatment.

Conclusions

We observed a different pattern of CD81 T‐cell and B‐cell levels in naïve HIV/HCV coinfected patients according to HCV virological status and their subsequent variations during HCV antiviral treatment. CD81 expression might influence HCV pathogenesis and response to HCV antiviral treatment.

     

Choosing event‐driven and daily HIV pre‐exposure prophylaxis – data from two European PrEP demonstration projects among men who have sex with men

IntroductionDaily and event‐driven PrEP are both efficacious in reducing the risk for HIV infection. However, the practice of event‐driven PrEP (edPrEP) is less well studied, in particular when provided as an alternative to daily PrEP. We studied regimen preferences and switches, and sexually transmitted infection (STI) incidence.MethodsWe analysed pooled data from two prospective cohort studies among MSM: Be‐PrEP‐ared, Belgium and AMPrEP, the Netherlands. In both projects, participants could choose between daily and edPrEP at three‐monthly study visits, when they were also screened for sexually transmitted infections including hepatitis C (HCV). We assessed the proportion choosing each regimen, and the determinants of choosing edPrEP at baseline. Additionally, we compared the incidence rates (IRs) of HCV, syphilis and chlamydia or gonorrhoea between regimens using Poisson regression. The study period was from 3 August 2015 until 24 September 2018.Results and discussionWe included 571 MSM, of whom 148 (25.9%) chose edPrEP at baseline. 31.7% of participants switched regimen at least once. After 28 months, 23.5% used edPrEP. Older participants (adjusted odds ratio (aOR) = 1.38 per 10 years, 95% confidence interval (CI) = 1.15 to 1.64) and those unemployed (aOR = 1.68, 95% CI = 1.03 to 1.75) were more likely to initially choose edPrEP. IR of HCV and syphilis did not differ between regimens, but the IR of chlamydia/gonorrhoea was higher among daily users (adjusted incidence rate ratio = 1.61, 95% CI = 1.35 to 1.94).ConclusionsA quarter of participants chose edPrEP at baseline and at 28 months this proportion was similar. Although the IR of HCV and syphilis were similar in the two regimens, the lower incidence of chlamydia and gonorrhoea among edPrEP users may suggest that less frequent STI testing of this group could be considered.     

Endothelium in pharmacology: 30 years on

In this issue, BJP is proud to publish an Endothelium Themed Section to celebrate the life of Robert F. Furchgott, who died on May 19th 2009. It is 30 years since he discovered endothelium-derived relaxant factor and a decade since he was awarded the Nobel Prize for this work. His discovery has led to an array of new therapeutic targets. The themed section includes three reviews on the pathophysiology of the endothelium and the drug targets that this presents, four research papers and three commentaries on research.This themed section also forms the nucleus of an online Virtual Issue that collects in one place further reviews and research papers on the topic of the ‘Endothelium’ that BJP and our sister journal BJCP have published in the past year, and that should help researchers and students to find the latest work in this field.To view the entire Endothelium Themed Section and the Endothelium Virtual Issue, please visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009British Journal of Pharmacology (2009) 157, 491–493; doi:10.1111/j.1476-5381.2009.00366.xThis article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009Thirty years ago Robert F Furchgott found that a substance was released from vascular endothelium that caused relaxation of the smooth muscle in the vascular wall (Furchgott and Zawadzki, 1980), a discovery for which, a decade ago, he was awarded the Nobel Prize (Furchgott, 1999). This remarkable finding was, from my recollection anyway, the most exciting aspect of the second Symposium on Mechanisms of Vasodilatation, held at Wilrijk, Belgium in July 1980 (Vanhoutte and Leusen, 1981) and has been, one suspects, a major part of the reason that this series is now celebrating its 10th occurrence at Matsushima, Miyagi, Japan, in June 2009 (it is planned to publish work arising from this event in Circulation Journal).Thirty years on, the endothelium continues to yield information on pathophysiological mechanisms that provides many therapeutic targets for drug discovery and new explanations for drug action. A special Endothelium Themed Section in this issue of BJP collates three new reviews on the pathophysiology of the endothelium and the drug targets that this presents (Esposito and Cuzzocrea, 2009; Grgic et al., 2009; Versari et al., 2009), four research papers (de Andrade et al., 2009; Andrews et al., 2009; McKenzie et al., 2009; Orie et al., 2009) and three commentaries on research papers that discuss the significance and draw out controversies from their new findings (Martin, 2009, commenting on Andrews et al., 2009; Tammaro, 2009, commenting on Orie et al., 2009; Miller and Wadsworth, 2009, commenting on Wenzl et al., 2009 that was published in an earlier issue).These Endothelium reviews and two others already published (Félétou, 2009; Félétou et al., 2009) follow up symposia held at the Meeting of the Federation of European Pharmacological Societies (EPHAR) in Manchester, UK, in July 2008, and show the continuing importance of this field. To reflect this and provide access to our extensive portfolio of endothelial papers, we have collated this section with other recent reviews, commentaries and original articles from BJP and from our sister journal BJCP, in a Virtual Issue on Endothelium, available at: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 (see http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009)

Irbesartan-mediated reduction of renal and cardiac damage in insulin resistant JCR : LA-cp rats

Background and purpose:

Angiotensin II receptor antagonists (ARBs), originally developed for antihypertensive properties, have pleiotropic effects including direct vascular actions. We tested the hypothesis that the ARB irbesartan would be effective against micro- and macrovascular complications of the prediabetic metabolic syndrome using the obese, insulin-resistant JCR : LA-cp rat that exhibits micro- and macrovascular disease with ischaemic myocardial lesions and renal disease.

Experimental approach:

Obese male rats were treated with irbesartan (30 mg·kg⁻¹·day⁻¹, incorporated into chow) from 12 to 25 weeks of age.

Key results:

Irbesartan treatment caused no change in food intake or body weight. Fasting glycaemic control of the JCR : LA-cp rats was marginally improved, at the expense of increased plasma insulin levels (∼50%). Fasting plasma triglycerides were marginally reduced (∼25%), while cholesterol concentrations were unchanged. Elevated concentrations of adiponectin, monocyte chemotactic protein-1 and plasminogen activator inhibitor-1 were reduced along with severity of glomerular sclerosis. Macrovascular dysfunction (aortic hypercontractile response to noradrenergic stimulus and reduced endothelium-dependent relaxation) was improved and frequency of ischaemic myocardial lesions reduced (62%).

Conclusions and implications:

Irbesartan reduces markers of inflammation and prothombotic status, improves macrovascular function and reduces glomerular sclerosis and myocardial lesions in a model of the metabolic syndrome. Unlike pharmaceutical agents targeted on metabolic dysfunction, irbesartan reduced end-stage disease without major reduction of plasma lipids or insulin. The protective effects appear to be secondary to unknown intracellular mechanisms, probably involving signal transduction pathways. Understanding these would offer novel pharmaceutical approaches to protection against cardiovascular disease.     

Identification of malaria hot spots for focused intervention in tribal state of India: a GIS based approach

Background  

In India, presently malaria shows a declining trend whereas Plasmodium falciparum (Pf) cases show an up trend. In central India, specifically, Madhya Pradesh (M.P.) a forested and tribal area, control of malaria is logistically difficult and outbreaks are frequently recorded, reasons for this being inadequate surveillance, poor reporting, a time lag in reporting to decision makers and a lack of geo referenced information to pin point the trouble spots for a timely preventive action.     

Prothrombin complex concentrate (Beriplex P/N) in severe bleeding: experience in a large tertiary hospital

Introduction

Major blood loss can often be life-threatening and is most commonly encountered in the settings of surgery and trauma. Patients receiving anticoagulant therapy are also at increased risk of bleeding. We investigated the use of a prothrombin complex concentrate (PCC; Beriplex P/N, CSL Behring, Marburg, Germany) to treat severe bleeding in a variety of settings: cardiac surgery, warfarin therapy and other surgery.

Methods

Thirty consecutive patients who had received PCC were identified from blood transfusion records. For cardiac surgery and warfarin reversal, PCC was administered in accordance with hospital protocols. PCC was administered to cardiac and other surgical patients responding poorly to recognized blood products, whereas it was administered first-line to patients with life-threatening bleeds and requiring warfarin reversal, in accordance with British Committee for Standards in Haematology guidelines. We conducted a retrospective analysis of patient records in order to ascertain PCC dose, use of other blood products and response to PCC (clotting screen results before and after PCC administration, haemostasis achievement, and survival).

Results

Six patients (20%) were excluded because of inadequate documentation (n = 5) or acquired haemophilia (n = 1). Therefore, 24 patients were included in the analysis: coronary artery bypass graft (n = 5), mitral/aortic valve replacement (n = 2), other surgery (n = 9) and warfarin reversal (n = 8). Most patients (83.3%) received no more than 1500 IU of Beriplex P/N 500. Considerable reduction in administration of other blood products was seen during the 24 hours after PCC administration. Partial or complete haemostasis was achieved in 14 out of 18 cases (77.8%). In total, 12 out of 24 patients (50%) died during the study; two-thirds of the deaths were considered unrelated to bleeding. No thrombotic complications or adverse drug reactions were observed.

Conclusion

This study emphasizes the value of PCC in reversing the effects of oral anticoagulant therapy in bleeding patients. It also demonstrates the potential value of PCC in controlling bleeding in patients undergoing cardiac and other surgical procedures. The use of PCC in bleeding patients without hereditary or anticoagulation-related coagulopathy is novel, and further investigation is warranted. In the future, it may be possible to use PCC as a substitute for fresh frozen plasma in this setting; adequate documentation is crucial for all blood products.